Allyl ethers

ABSTRACT

ALLYL ETHERS OR ESTERS OF ALIPHATIC ALCOHOLS OR ACIDS WHEREIN THE ALIPHATIC CHAIN CONTAINS AN EPOXIDE GROUP AND AT LEAST 7 CARBON ATOMS. THE ETHERS AND ESTERS ARE USEFUL IN KILLING AND PREVENTING THE PROLIFERATION OF INSECTS BY UPSETTING THEIR HORMONAL BALANCE.

" ALLYL ETHERS Madhukar Subraya 'Choduekan'Basel, Albert Pfifiner,Pfalfhausen, N'orbert 'Rigassi, Arlesheim, Ulrich Schwieter, Reinach,and Milos Suchy, Basel, Switzerland, assignors to Hoffman-La Roche Inc.,Nutley,

. NJ. l y 1 Y No Drawing. Filed Jan. 21, 1971, Ser. No..108,599

- Int. Cl. C07d 1/18 0.5. Cl. 260-348 R 8 Claims ABSTRACT on THEDISCLOSURE Allyl ethers or esters of aliphatic alcohols or acids whereinthe aliphatic chain contains an epoxide group and atleast 7 carbonatoms. The ethers and esters are useful in killing and preventing theproliferation of insects by upsetting their hormonal balance.

SUMMARY OF THE INVENTION In accordance with this invention, it has beenfound that compounds of the formula:

wherein R is methyl or ethyl; R R and R are hydrogen, methyl or ethyl;'R is hydrogen or methyl;

R R and R are hydrogen, lower alkyl, lower alkenyl,

lower alkynyhlower aryl or lower aryl-lower alkyl;

X is

R is hydrogen, methylor ethyl; and m and n are integers of 0 to l; upsetthe hormone balance of pests such as insects to prevent .them fromgrowing and reproducing.

The compounds of Formula I are prepared by epoxidizing a compound of theformula:

The compounds of Formula I are also prepared through thedehydrohalogenation of a halohydrin of the formula:

3,781 ,309 Patented Dec. 25, 1973 ice .The compounds of Formula I arefurther prepared by reacting a compound of the formula:

R1 R4 RI om-o ozcm-om-hon onr wherein R R R R R R R R m and n are asabove; one of K and J is chlorine, bromine or iodine and the other is analkali salt of the hydroxyl group; and R is individually hydrogen and Rindividually is hydrogen, methyl or ethyl or R and R taken together forman additional carbon-carbon bond;

to give a compound of the formula:

Jill

3 10 Ra Ra (urinal ama a wherein R1, R2, R3, R4, R5, R R7, R R9, R10, mand n are as above.

In the case where R and R in the compound of Formula VI form a carbon tocarbon bond, this compound may be partially hydrogenated to a compoundof Formula I wherein both R and R are hydrogen. The compounds of FormulaI are still further prepared by wherein R is lower alkyl, phenyl,halophenyl and loweralkoxyphenyl; and R R R R and R are as above;

to give a compound of the formula:

wherein R R R R R R R R R and m areas above.

In the case where R and R in the compound of Formula -IX form a carbonto carbon bond, this compound can be partially hydrogenated to acompound of Formula I wherein both R and R are hydrogen.

3 v DETAILED DESCRIPTION OF THE INVENTION The term halogen or halo, asused throughout this application, when not expressly stated otherwise,includes all four halogens, i.e., bromine, chlorine, fluorine andiodine. As used throughout this application, the term lower alkylcomprehends both straight-chain and branched chain saturated alkylhydrocarbon groups containing from 1 to 6 carbon atoms, such as methyl,ethyl, propyl, ispropyl, etc. The term lower alkenyl, as used herein,includes both straight and branched chain unsaturated alkenylhydrocarbon groups having from 2 to 6 carbon atoms, such as vinyl,allyl, butenyl, pentenyl, and the like. The term lower alkynyl, as usedherein, includes both straight and branched chain, acetylenicunsaturated hydrocarbon having from 2 to 6 carbon atoms such as ethynyl,propargyl, butynyl, etc.

The term lower aryl, as used throughout the application, signifiesmono-nuclear, aromatic hydrocarbons such as phenyl, tolyl, etc. whichcan be unsubstituted or substituted in one or more positions with alower alkylenedioxy, a halogen, a nitro, a lower alkyl, a lower alkoxy,a lower alkynyl, a lower alkynyloxy, a lower alkenyl or a loweralkenyloxy substituent, and polynuclear aryl groups such as naphthyl,anthryl, phenanthryl, azulyl, etc. which may be substituted with one ormore of the aforementioned groups. The preferred lower aryl group isphenyl which can be either unsubstituted or substituted with one of theaforementioned groups. The term lower aryl-lower alkyl comprehends loweraryl-lower alky groups wherein aryl is defined as above and the alkyl islower alkyl. The preferred lower aryl-lower alkyl group is benzyl. Thelower aryl moiety of the lower aryl-lower alkyl group can be eitherunsubstituted or substituted with one of the aforementioned groups.

As used herein, the term lower alkylenedioxy designates loweralkylenedioxy groups having 1-4 carbon atoms such as methylenedioxy andethylenedioxy. As used herein, the term lower alkoxy comprehends loweralkoxy groups containing from 1 to 6 carbon atoms, such as methoxy,propoxy, ethoxy, etc. The term lower alkenyl oxy, as utilized herein,comprehends lower alkenyloxy groups wherein lower alkenyl is defined asabove. Among the preferred lower alkenyloxy groups are includedvinyloxy, allyloxy, butenyloxy and pentenyloxy. The term alkynyloxy, asused herein, comprehends the lower alkynyloxy groups wherein loweralkynyl is defined as above.

The compounds of Formula I are useful in the control of pests such asEphestia Kuniella (flour moth) and Tenebrio molitor (yellow meal worm).In contrast to most of the known pest-control agents which kill, disableor repell the pests by acting as contract-poisons and feedpoisons, thecompounds of Formula I above prevent maturation and proliferation ofthese pests by interfering with their hormonal system. In insects, forexample, the transformation to the imago, the laying of viable eggs andthe development of laid normal eggs is distrubed. Furthermore, thesequence of generations is interrupted and the insects are indirectlykilled.

The compounds of Formula I above are practically nontoxic tovertebrates. The toxicity of the compounds of Formula I is greater than,1,000 mg./kg. body weight. Moreover, these compounds are readilydegraded and the risk of accumulation is therefore excluded. Therefore,these compounds can be used without fear of danger in the control ofpests in animals; plants; foods; and textiles.

Generally, in controlling invertebrate animals, the compounds of FormulaI above are applied to the material to be protected, e.g., foodstuffs,feeds, textiles, plants in amounts of from about l0 to 10- gm./cm.Generally, it is preferred to utilize the compounds of Formula 1 abovein a composition with a suitable inert carrier. Any

conventional inert carrier can be utilized. Such a composition containsone or more compounds of Formula I in a concentration from about 0.01%to about 0.5%, preferably 0.1%.

The compounds of Formula I can, for example, be used in the form ofemulsions, suspensions, dusting agents, solutions or aerosols. Inspecial cases, the materials to be protected (e.g., foodstuffs, seeds,textiles and the like) can also be directly impregnated with theappropriate compound or with a solution thereof. Moreover, the compoundscan also be used in a form which only releases them by the action ofexternal influences (e.g., contact with moisture) or in the animal bodyitself.

The compounds of Formula I above can be used as solutions suitable forspraying on the material to be protected which can be prepared bydissolving or dispersing these compounds in a solvent such as mineraloil fractions; cold tar oils; oils of vegetable or animal origins;hydrocarbons such as na-pthalenes; ketones such as methyl ethyl ketone;or chloroinated hydrocarbons such as tetrachloroethylene,tetrachlorobenzene, and the like. The compounds of Formula I above canalso be prepared in forms suitable for dilution with water to formaqueous liquids such 'as, for example, emulsion concentrates, pastes orpowders. The compounds of Formula I above can be combined with solidcarriers for making, dusting or strewing powders as, for example, talc,kaolin, bentonite, calcium carbonate, calcium phosphate, etc. Thecompositions containing the compounds of Formula I above can contain, ifdesired, emulsifiers, dispersing agents, wetting agents, or other activesubstances such as fungicides, bacteriacides, nematocides, fertilizersand the like. The materials which are to be protected act as bait forthe insect. In this manner, the insect, by contacting the materialimpregnated with a compound of Formula I above, also contacts thecompound itself.

In accordance with this invention, the preferred compounds of Formula Iabove are those where R R and R are hydrogen, lower alkyl, loweralkenyl, lower alkynyl, lower aryl, or lower aryl-lower alkyl, where thelower aryls may be unsubstituted or substituted in one or more positionswith a halogen, a lower alkyl, a lower alkyloxy or a nitro substituent.Particularly preferred are compounds of Formula I above where: R R and Rare hydrogen, lower alkyl, lower alkenyl, lower alkynyl and lower aryl.

Among the most preferred compounds of Formula I above are included:

1-(allyloxy)-4,5-epoxy-1,S-dimethyl-hexane;

l-(allyloxy)-6,7-epoxy-3,7-dimethyl-2-octene;

1-(allyloxy)-10,11-epoxy-3,7,11-trimethyl-2,6-

dodecadiene;

1-(al1yloxy)-10,l1-epoxy-3,7,1l-trimethyl-2,6-

tridecadiene;

1-(ally1oxy)-l0,1 1-epoxy-7-ethyl-3,l1-dimethyl-2,6-

tridecadiene;

1- 1- (3,4-methylenedioxy-phenyl) -allyloxy] -6,7-epoxy-3,6,7-trimethyl-2-octene;

10,1 1-epoxy-3,7,10,1 1-tetran1ethyl-2,6-dodecadienoic acid allyl ester;

10,1 1-epoxy-3,7,11-trimethyl-2,6-dodecadienoic acid allyl ester;

10,1 1-epoxy-7-ethyl-3,1 1-dimethyl-2,6-tridecadienoic acid allyl ester;7

6,7-epoxy-3,7-dimethyl-2-octenoic acid allyl ester;

l- 1,1-dimethyl-allyloxy) -6,7-epoxy-3,7-dimethyl-2- octene;

10,l1-epoxy-3,7,1l-trimethyl-[(3-methyl-2,4-pentadienyl)-oxy]-2,6-dodecadiene;

10,1'1-epoxy-3,7,1l-trimethyl-[3-methyl-2-penten-4-ynyl)-oxy]-2,6-dodecadiene; and

10,1 l-epoxy-3,7,l l-trimethyl-2,6-dodecadienoic acid3-methyl-2-penten-4-ynyl ester.

Among the starting materials which can be utilizedto prepare thecompounds of Formula I are included:

allyl 1,5-dimethyl-4-hexenyl ether;

allyl 3,7-dimethyl-2,6-octadienyl ether;

3,7,11-trimethyl-2,6,l0-dodecatrienoic acid allyl ester;

3,7,1l-trimethyl-2,6,IO-tridecatrienoic acid allyl ester;

3,7-dimethyl-2,fi-octadienoic acid allyl ester;

3,7-dimethyl-2,6-octadienyl 1,1-dimethyl-allyl ether;

allyl 3,7,11-trimethyl-2,6,10-dodecatrienyl ether; and

3-methyl-2,4-pentadienyl 3,7,1 l-trimethyl-2,6, 1 0- dodecatrienylether;

allyl 7-ethyl-3,11-dimethyl-2,6,IO-tridecatrienyl ether.

One method for preparing a compound of Formula I above involvesepoxidizing a compound of Formula II in an inert solvent with a peracid.For this purpose, a compound of Formula II is dissolved in an inertsolvent. Any conventional inert solvent may be utilized, withhalogenated hydrocarbon solvents such as chloroform or carbontetrachloride being preferred and methylene chloride being especiallypreferred. Although temperature and pressure are not critical, thisreaction is preferably carried out at a temperature of from about 0 C.to about 40 C. Any conventional peracid can be utilized. Among thepreferred peracids are included performic acid, peracetic acid,perbenzoic acid, perphthalic acid or pertungstic acid, withm-chloroperbenzoic acid being especially preferred.

Another method for preparing a compound of Formula I above involvesdehydrohalogen-ation a compound of Formula III above with a base. Forthis purpose, the compound of Formula III is dissolved in a conventionalsolvent, preferably in an alkanol where X is an oxymethylene group,methanol being especially preferred, or in an ether where X is acarbonyl group, diethyl ether being especially preferred. Anyconventional base can be utilized, but the alkali metal alcoholates arepreferred where X is an oxymethylene group, sodium methylate beingespecially preferred, and pulverized alkali hydroxides or potassiumcarbonate are preferred where X is a carbonyl group, potassium andsodium hydroxides being especially preferred. Although temperature andpressure are not critical, the reaction is preferably carried outbetween about 0 C. and 40 C. The epoxide of Formula I is thus obtainedin a smooth reaction.

The above method, involving the compounds of Formula III as a reactant,offers the advantage that, with esters and ethers, only the terminaldouble bond is epoxidized. By contrast, in making compounds of Formula Ihaving more than one double bond from the compounds of Formula II, theterminal double bond is not selectively converted into the correspondingepoxide using a peracid. Rather, a mixture of epoxides is generallyobtained using a peracid which can be separated in a manner known per seby chromatography.

A further method of preparing compounds of Formula I of the instantinvention involves reacting the compounds of Formula IV with thecompounds of Formula V. This reaction is generally carried out in anyconventional inert organic solvent. Preferred inert organic solvents arebenzene, toluene, tetrahydrofuran, dioxane, 1,2-dimethoxyethane, withtetrahydrofuran being especially preferred. To the reaction mixture isadded an aprotonic solvent. Any conventional aprotonic solvent can beutilized, but hexamethyl phosphoric acid triamide is especiallypreferred. In carrying out this reaction, temperature and pressure arenot critical, and any temperature of from about 0 C. to about theboiling point of the solvent can be utilized. Generally, the reaction ispreferably carried out at the reflux temperature of the reactionmixture. In a particularly preferred embodiment, the invention iscarried out in tetrahydrofuran at the reflux temperature which is 70 C.In carrying out this reaction, the hydroxyl group on either of thecompounds of Formula IV or V is initially converted by conventionaltechniques, in an inert solvent, into an alkali metal salt. One methodof converting to the alkali metal salt is by reacting the compound ofeither Formula IV or V, where either I or K is a hydroxyl group with asuitable base such as an alkali metal hydride, eg sodium hydrideutilizing tetrahydrofuran as a solvent. This alkali metal salt is thenreacted with the halide of either Compound IV or V to yield Compound VI.

A still further method for preparing a compound of Formula I of theinstant invention involves reacting a carbonyl compound of Formula VIIwith a phosphine oxide of Formula VIII to obtain a compound of FormulaIX. Although temperature and pressure are not critical, this reaction ispreferably effected in a temperature range of 0 C. to about 40 C. Thereaction is carried out in the presence of a base and in an inertorganic solvent. Any conventional base and inert organic solvent can beutilized in this reaction. The preferred bases are, however, the alkalimetal hydrides, such as sodium hydride, preferably dissolved in benzene,toluene, dimethylformamide,

' tetrahydrofuran, dioxane or 1,2-dimethoxyethane and the alkali metalalcoholates, such as sodium methylate, preferably dissolved in analcohol, such as methanol. In a particularly preferred reaction, acompound of Formula VII is reacted with a phosphine oxide of FormulaVIII in the presence of 2 moles of sodium hydride in absolutetetrahydrofuran, excess sodium hydride being decomposed by addingabsolute alkanol prior to the working up.

When R and R form an additional carbon to carbon bond in compounds ofFormula VI or IX, the compounds of Formula I can be formed by selectivehydrogenation of the acetylenic bond in the compound of Formula VI or IXto an olefin double bond. For this purpose, the acetylenicallyunsaturated compound is dissolved in an inert solvent, preferably ahigh-boiling petroleum ether, and is partially hydrogenated in thepresence of a partially inactivated catalyst, such as a lead/palladiumcatalyst deactivated with quinoline; Helv. Chim Acta 35, 446 (1952);Hoppe-Seylers Z. Phsiol. Chem. 295, 290 (1935).

The starting materials of Formula II, used in the process in accordancewith the instant invention, can be obtained according to severalprocedures. One method of obtaining compounds of Formula II wherein X isoxymethylene consists of reacting a compound of the formula:

wherein 1 2, 3 4, 5, 6 7 a 9, 10, m and n are as above and one of K andJ' is a halogen and the other is an alkali salt of the hydroxy group.

This reaction is carried out in the same manner as described hereinabovewith respect to reacting compounds of Formula IV with compounds ofFormula V. This reaction can be effected in any conventional inertorganic solvent, preferably benzene, toluene, dioxane,1,2-dimethoxyethane or tetrahydrofuran. Although the temperature andpressure of the reaction is not critical, a temperature range lyingbetween 0 C. and the boiling point of the solvent concerned ispreferred. An aprotonic solvent such as hexamethyl phosphoric acidtriamide is preferably also added to the reaction mixture.

One method of obtaining compounds of Formula II wherein X is oxycarbonylconsists of reacting a compound of the formula:

VlI-A wherein R R R R and m are as above;

with a compound of Formula VIII. This reaction is carried out in thesame manner as described hereinabove with respect to reacting compoundsof Formula VII with compounds of Formula VIII. This reaction isexpediently carried out in the presence of a base, preferably dissolvedin an inert organic solvent.

Another method for obtaining compounds of Formula 11 wherein X isoxycarbonyl consists of esterifying an acid of the formula:

wherein R R R R m and n are as above;

with a compound of Formula V wherein J is a hydroxyl group. Any of theconventional methods of esterifying an acid with an alcohol can beutilized in carrying out this reaction. In accordance with a preferredembodiment of this invention, the acid of Formula X is reacted with ahalogenating agent, such as thionyl chloride, thionyl bromide,phosphorous trichloride, phosphorous oxychloride, etc., with thionylchloride being preferred. The halogenation of the acid of Formula X iscarried out in the presence of an inert organic solvent, such aspetroleum ether, benzene, hexane, etc. within a temperature range fromabout C. to about the boiling point of the reaction mixture. Thishalogenation reaction is carried out in the presence of an organic aminebase. Any of the conventional organic amine bases such as pyridine,triethylamine, quinoline, etc. can be used, but pyridine is preferred.The resulting acid halide can then be reacted by conventional means Withthe compound of Formula V, wherein I is a hydroxy group, to produce thecompound of Formula II, wherein X is oxycarbonyl. Generally, thisreaction is carried in an inert organic solvent, such as benzene,toluene, hexane, iso-octane, chloroform, carbon tetrachloride orethylene glycol dimethyl ether within a temperature range from about 0C. to about the boiling point of the reaction mixture. This reaction isalso carried out in the presence of an acid binding agent such aspyridine, triethyl amine, quinoline, with pyridine being preferred, togive the desired allyl or propargyl ester. The propargyl ester can bepartially hydrogenated to a compound of Formula H.

Starting compounds of Formula III are obtained by hydroxy-halogenating acompound of Formula H. This hydroxyhalogenation can be carried out byconventional procedures. In accordance with a preferred embodiment ofthis invention, the compound of Formula H is suspended in water andtreated with an equal amount of an inert organic solvent to form ahomogeneous, concentrated solution. Any conventional inert organicsolvent such as tetrahydrofuran, dioxane, 1,2-dimethoxyethane, etc.,preferably tetrahydrofuran can be utilized. This solution can be treatedwith a conventional hydroxyhalogenating agent to hydroxyhalogenate thecompound of Formula II. If, for example, a compound of Formula III isdesired wherein Z is bromine, N-bromo-succinimide is introducedportionwise into such a solution in a temperature range of from about 0C. to 40 C. If compounds of Formula III are desired wherein Z ischlorine or iodine, N-chloro-succinimide or N-iodo-succinimide iscorrespondingly used. A preferred temperature range for carrying outthis reaction lies between 0 C. and 5 C.

The compounds of Formula I of the instant invention exist as a cis/transisomer mixture. The mixture can, for example, be separated into theisomeric forms by adsorption on a material with selective activity. Forexample, the isomer mixture can be dissolved in an inert organicsolvent, such as hexane, diethyl ether or acetic acid ethyl ester, andadsorbed on Kieselgel. The isomers adsorbed in different zones can beeluted with one of the solvents or solvent mixtures mentionedhereinbefore and isolated. The isomer mixture can, in individual cases,also be separated by fractional distillation or optionally preparativethin layer chromatography.

The following examples illustrate the invention. All temperatures arestated in degrees centigrade. Nujol is mineral oil, and the percent ofhydride in the mineral oil suspension is given as percent by weight.

Example 1 2.4 g. of sodium hydride (50% Nujol suspension) is washedtwice with hexane and overlaid with 10 ml. of absolute tetrahydrofuranand, with stirring and ice-cooling, 11.9 g. of10,1l-epoxy-3,7,1l-trimethyl-Z-cis/trans, 6-cis-dodecadien-l-ol in 10ml. of absolute tetrahydrofuran is added dropwise, and the mixture isfurther stirred at room temperature for 1 hour. With ice-cooling, 7 g.of allyl bromide and 20 ml. of hexamethyl phosphoric acid triamide aresuccessively added dropwise, and the mixture is further stirred at 50 C.for 3 hours. The cooled reaction mixture is poured onto ice-water andexhaustively extracted with hexane. The combined hexane extracts areworked up by washing with saturated aqueous sodium chloride solution,followed by drying over sodium sulphate and then filtering andevaporating. After working up in the preceding manner, the residues arechromatographed on Kieselgel with hexane and acetic ester (4:1 parts byvolume) to yield pure l-( allyloxy)-10,11-epoxy-3,7,1l-trimethyl-Z-cis/trans, 6-cis-dodecadiene. A sample is distilledin the bulb-tube. Boiling point ca. l20/10- mm. Hg; n =1.4785.

Example 2 A solution of 4.4 g. of sodium in 95.5 ml. of absolutemethanol is added dropwise with ice-cooling to a solution of 73 g. of3-bromo-2,6,lO-trimethyl-IZ-[(trans-3-methyl- 2-penten-4-ynyl) -oxy]-6-cis, 10-cis/trans-dodecadien-2-o1 in 95.5 ml. of absolute methanoland the mixture is subsequently further stirred for 0.5 hours. Thereaction mixture is poured onto ice-water, exhaustively extracted withdiethyl ether and Worked up as described in Example 1. By chromatographyon Kieselgel with hexane and diethyl ether (4:1 parts by volume), thereis obtained pure 10,1 1 epoxy-3,7,1 l-trimethyl- 1-(trans-3-methyl-2-penten-4-ynyl)-oxy]-2-cis/trans, 6-cis-dodecadienewhich decomposes on distillation in high vacuum. A sample is distilledin the bulb-tube; boiling point ca 140145/10- mm. Hg; n =1.4974.

The starting material is obtained as follows:

39 g. of sodium hydride (50% Nujol suspension) is Washed twice withhexane and overlaid with 400 ml. of tetrahydrofuran, and, with stirringand ice-cooling, 78.2 g. of trans-3-methyl-2-penten-4-yn-l-ol is addeddropwise, and the mixture is further stirred at room temperature for 1hour. 232 g. of Z-cis/trans, -cis-farnesyl bromide and 270 ml. ofhexamethyl phosphoric acid triamide are subsequently successively addeddropwise, and the mixture is stirred at 50 for 3 hours and worked up asdescribed in Example 1. By chromatography on Kieselgel with hexane anddiethyl ether (97.5:2.5 parts by volume), there is obtained puretrans-3-methyl-2-penten- 4-ynyl 3,7,1l-trimethyl-Z-cis/trans, 6-cis,10-dodecatrienyl ether. A sample is distilled in the bulb-tube. Boilingpoint ca 127/0.0015 mm. Hg; n =l.5012.

89.3 g. of N-bromosuccinimide is added portionwise with ice-cooling to ahomogeneous solution of 134 g. of trans 3 methyl-2-penten-4-ynyl3,7,11-trimethyl-2-cis/ trans, 6-cis, IO-dodecatrienyl ether in 1300 ml.of tetra- -hydrofuran and 208 m1. of water. The, mixture is further.stirred for 4 hours with ice-cooling and worked up as described inExample 1. By chromatography on Kieselgel with hexane and diethyl ether(4:1. parts by volume), there is obtained pure3-bromo-2,6,10-trimethyl-12- [(trans 3--methyl-2-penten-4-ynyl)-oxy]-6-cis-l0-cis/ trans-dodecadien-Z-ol whichdecomposes on distillation in high vacuum. n =L5213 (sample dried inhigh vacuum at 50 for 3 hours).

Example 3 0.6 ml. of quinoline and 0.6 g. of Lindlar catalyst are addedto a solution of 6 g. of 10,11-epoxy-3,7,11-trimethyl-1-[(trans-3-methyl-2-penten-4 ynyl)-oxy] 2 cis/ trans, -6-cis-dodecadienein 60 ml. of petroleum ether (B.P. 80-110 C.), and the mixture ishydrogenated up to the uptake of the theoretical amount of hydrogen,filtered from the catalyst and evaporated. In order to remove thequinoline, the reaction mixture is worked up by chromatographing onKieselgel with hexane and diethyl ether (4:1 parts by volume) and asample distilled in the bulb-tube. There is obtainedl0,11-epoxy-3,7,1l-trimethyl- (trans-3-methyl-2,4-pentadienyl) -oxy]-2-cis/ trans, 6-cisdodecadiene. Boiling point ca 120"/10' mm. Hg; n

Example 4 Example 5 43.3 g. of m-chloroperbenzoic acid are addedportionwise with ice-cooling to a solution of 33 g. of allyl 3,7-dimethyl-Z-cis/trans, 6-octadienyl ether in 350' ml. of methylenechloride, and the mixture is further stirred with ice-cooling for 2hours, subsequently diluted with 250 ml. of methylene chloride andsuccessively washed with ice-cold l-N caustic soda and saturated aqueoussodium chloride, dried over sodium sulphate, filtered and evaporated. Bychromatography on Kieselgel with hexane and diethyl ether (4:1 parts byvolume) and subsequent distillation, there is obtained pure1-(allyloxy)-6,7-epoxy- 3,7-dimethyl-2-cis/trans-octene; boiling point7072/0.1

mm. Hg; n =1.4633.

The starting material is obtained as follows:

48 g. of sodium hydride (50% Nujol suspension) is washed twice withhexane and subsequently overlaid with 500 ml. of absolutetetrahydrofuran. With stirring and ice-cooling, 58 g. of allyl alcoholis added dropwise and the mixture is stirred at room temperature for 1hour. With ice-cooling, 220 g. of 2-cis/trans-geranyl bromide and 400ml. of hexamethyl phosphoric acid triamide are successively addeddropwise, and the mixture is heated at reflux for 3 hours. The mixtureis subsequently worked up as described in Example 1 and fractionallydistilled. Boiling point 51/0.015 mm. Hg; n =1.4695.

Example 6 9 g. of m-chloroperbenzoic acid (93%) is added portionwisewith ice-cooling to 9.3 g. of 2-cis/trans-geranium acid allyl ester in100 ml. of methylene chloride, and the mixture is further stirred withice-cooling for 2 hours. The mixture is then worked up by being dilutedwith 100 ml. of methylene chloride, washed initially with icecold 1-Ncaustic soda and thereafter with saturated aqueous sodium chloridesolution, dried over sodium sulphate, filtered and evaporated. Afterbeing worked up in the preceding manner, the residues arechromatographed on Kieselgel with hexane and diethyl ether (4:1 parts byvolume) and subsequent distilled to obtain pure 6,7-epoxy-3,7-dimethyl-Z-cis/trans-octenoic acid allyl ester; boiling point8184/0.05 mm. Hg; n =1.4728.

The starting material is obtained as follows:

20.2 g. of thionyl chloride is added dropwise with icecooling to asolution of 25.2 g. of geranium acid and 13.5 g. of pyridine in 150 ml.of absolute ether, and the mixture is stirred at room temperature for 1hour with the exclusion of moisture. The precipitated pyridinehydrochloride is rapidly filtered off, rinsed with hexane and thereaction solution evaporated in vacuum. The unpurified geranium acidchloride is taken up in ml. of absolute benzene and, with ice-cooling,added dropwise to a solution of 9.3 g. of alcohol and 13.5 g. ofpyridine in 200 ml. of hexane and 80 ml. of benzene and further stirredat room temperature for 1 hour. The reaction mixture is poured ontoice-cold, dilute hydrochloric acid, the organic phase is separated oil,and the aqueous-hydrochloric acid phase is extracted twice with hexane.The combined organic phases are successively washed neutral withsaturated aqueous sodium bicarbonate solution and saturated aqueoussodium chloride solution, dried over sodium sulphate, filtered ofi andevaporated. By chromatography on Kieselgel with hexane and diethyl ether(9:1 parts by volume) and subsequent distillation, there is obtainedpure Z-ciS/trans-geranium acid allyl ester; boiling point 70/ 0.01 mm.Hg; n =1.4800.

Example 7 trans-dodecadienoic acid trans-3-methyl-2-penten-4-ynyl esterobtained boils in the bulb-tube with decomposition at ca. 150/10- mm.Hg; n =1.5020.

The starting material is obtained as follows:

24.6 g. of 3,7,1l-trimethyl-Z-cis/trans, 6-trans, 10-dodecatrienoic acidchloride in 70 ml. of absolute benzene is added dropwise withice-cooling to a solution of 9.6 g. of trans-3-methyl-2-penten-4-yn-l-oland 8.15 ml. of absolute pyridine in 200 ml. of hexane and 55 m1. ofabsolute benzene, further stirred at room temperature for 1 hour andworked up and chromatographed as described in Example 6, second part. Asample of the pure 3,7,11-trimethyl-2-cis/trans, 6-trans,IO-dodecatrienoic acid trans- 3-methyl-2-penten-4-ynyl ester boils inthe bulb-tube at ca. "/l0 mm. Hg; n =1.5098.

Example 8 11.5 g. of m-chloroperbenzoic acid is added portionwise withice-cooling to 12.5 g. of 3,7-dimethyl-2,6-octadienyl1,1-dimethyl-2-propenyl ether in 130 ml. of methylene chloride. Themixture is stirred for 2 hours, thereafter diluted with 130 ml. ofmethylene chloride and successively washed with ice-cold l-N causticsoda and saturated aqueous sodium chloride solution, dried over sodiumsulphate and evaporated. The residue is chromatographed on Kieselgelwith hexane and diethyl ether (9:1 parts by volume). There is obtainedpure 6,7-epoxy-3,7- dimethyl 1 [(l,1-dimethyl-2-propenyl)-oxy-2-octene.Boiling point 80/0.15 mm. Hg; n =1.4619.

The starting material is obtained as follows:

9.6 g. of sodium hydride (50% Nujol suspension) is washed twice withhexane and overlaid with 80 m1. of absolute tetrahydrofuran. Withice-cooling, 17.2 g. of 2- methyl-3-buten-2-ol in ml. of absolutetetrahydrofuran is added dropwise, and the mixture is stirred at roomtemperature for 1 hour. 23 g. of geranyl bromide and thereafter, withoccasional ice-cooling, 80 ml. of hexamethyl phosphoric acid triamideare subsequently added dropwise, and the mixture is heated at reflux for2 hours. The cooled reaction mixture is poured onto saturated aqueoussodium chloride solution, worked up as described in Example 1, andchromatographed on Kieselgel with hexane and diethyl ether (95:5 partsby volume). The 3,7-dimethyl-2,6-octadienyl 1,1-dimethyl-2-propenylether boils at 58- 59/0.08 mm. Hg; n =1.4673.

Example 9 2.5 g. of m-chloroperbenzoic acid (93%) is added portionwisewith stirring and ice-cooling to 3.8 g. of 3,6,7- trimethyl-1-[(u-vinylpiperonyDoxy] 2 cis/ trans, 6-octadiene in 40 ml. of methylenechloride, and the mixture is further stirred with ice-cooling for 2hours. The reaction mixture is subsequently diluted with 40 ml. ofmethylene chloride and washed with ice-cold l-N caustic soda andsaturated aqueous sodium chloride solution, dried over sodiumsulphateand evaporated. By chromatography on Kieselgel with hexane anddiethyl ether (4:1 parts by volume), there is obtained pure6,7-epoxy-3,6,7-trimethyl- 1-[(ot-vinylpiperonyl)oxy] 2cis/trans-octene. A sample boils in the bulb-tube at ca. 135 0.001 mm.Hg; n =1.5230.

The starting material i obtained as follows:

4.4 g. of sodium hydride (50% Nujol suspension) is washed with hexaneand overlaid with 40 ml. of absolute tetrahydrofuran. With ice-cooling,16 g. of a-ethynylpiperonyl alcohol in 120 ml. of absolutetetrahydrofuran is added dropwise, and the mixture is further stirred atroom temperature for 1 hour. 21 g. of 3,6,7-trimethyl-2- cis/ trans,6-octadienyl-1-bromide and 40 ml. of hexamethyl phosphoric acid triamideare subsequently successively added dropwise with ice-cooling, and themixture is stirred at room temperature for 1 hour, poured onto saturatedaqueous sodium chloride solution, and exhaustively extracted withdiethyl ether. The ether solution is washed with saturated aqueoussodium chloride solution, dried and evaporated. By chromatography onKieselgel with hexane and diethyl ether (9:1 parts by volume), there isobtained pure 3,6,7-trimethyl-l-[u-ethynylpiperonyDoxy]- 2-cis/trans,6-octadiene; n '=1.5366.

0.7 ml. of quinoline and 0.7 g. of Lindlar catalyst are added to 6.6 g.of 3,6,7-trimethyl-l-[(a-ethynylpiperonyl) oxy]-2-cis/trans, 6-octadienein 60 ml. of high-boiling petroleum ether-acetic ester (3:1), and themixture is hydrogenated up to the uptake of the theoretical amount ofhydrogen. The reaction solution is subsequently filtered off from thecatalyst and successively washed with ice-cold aqueou l-N hydrochloricacid, with aqueous sodium bicarbonate solution and saturated aqueoussodium chloride solution and dried over sodium sulphate and evaporated.By chromatography on Kieselgel with hexane and diethyl ether (85:15parts by volume), there is obtained pure3,6,7-trimethyl-1-[(a-vinylpiperonyD-oxy] 2 cis/ trans, -6-octadiene. Asample boils in the bulb-tube at ca. 82/6 mm. Hg; n =1.4388.

Example 10 14.6 g. of m-chloroperbenzoic acid (93%) is added portionwisewith stirring and ice-cooling to 12 g. of allyl 1,5- dimethyl-4-hexenylether in 120 ml. of methylene chloride, and the mixture is furtherstirred with ice-cooling for 1 hour. The reaction mixture issubsequently diluted with 120 ml. of methylene chloride and washed withice-cold 1-N caustic soda and saturated aqueous sodium chloridesolution, dried over sodium sulphate and evaporated. By chromatographyon Kieselgel with hexane and diethyl ether (9:1 parts by volume), thereis obtained pure 1- (al1yloxy)-4,5-epoxy-1,5-dimethyl-hexane. Boilingpoint ca. 80/0.005 mm. Hg; n =1.5230.

The starting material is obtained a follows:

9.6 g. of sodium hydride (50% Nujol suspension) is washed with hexaneand overlaid with 100 ml. of absolute tetrahydrofuran. With ice-cooling,25.4 g. of 6-methyl-5-hepten-2-ol is added dropwise, and the mixture isfurther stirred at room temperaturefor 1 hour. 24.2 g. of allyl bromideand 70 ml. of hexamethyl phosphoric acid triamide are subsequentlysuccessively added dropwise, and the mixture is stirred at roomtemperature for 16 hours, poured onto ice-water, exhaustively extractedwith diethyl ether, washed with saturated aqueous sodium chloridesolution and evaporated. By chromatography on Kieselgel with hexane anddiethyl ether (9:1 parts by volume) and subsequent distillation, thereis obtained pure allyl 1,5-dimethyl-4-hexenyl ether. Boiling point 6364/7 mm. Hg; n =1.4442.

Example 11 To a solution of 5.8 g. 1-(propynyloxy)-10,ll-epoxy-3,7,10,1l-tetramethyl-2,6-dodecadiene (cis and trans-mixture) in 60 ml.of high-boiling petroleum ether is added. .6 ml. of quinoline and .6 g.of Lindlar catalyst. The mixture is hydrogenated up to the uptake of thetheoretical amount of hydrogen, filtered to remove the catalyst, andthen evaporated to dryness. In order to remove the quinoline, thereaction mixture is chromatographed on Kieselgel with hexane and diethylether (4:1 parts by volume) and distilled. There is obtained1-(allyloxy)-lO,11-cpoxy 3,7,10,11-tetramethyl-2,-6-dodecadiene (cis andtrans-mixture). Boiling point -116 C./0.035 mm. Hg; n 1.4779.

Example 12 To a mixture of 10 g. 3-bromo-2,6,10-trimethyl-12-allyloxy-6,IO-dodecadien-Z-ol (cis and trans-mixture) in 14 ml. absolutemethanol is added dropwise, with ice-cooling, a solution of 645 mg.sodium in 14 ml. absolute methanol and the mixture is subsequentlyfurther stirred for 1 hour. The reaction mixture is poured ontoice-water, exhaustively extracted with diethyl ether, and worked up asdescribed in Example 1. By chromatography on Kieselgel with hexane anddiethyl ether (4:1 parts by volume), there is obtained pure 1 (allyloxy)10,11-epoxy 3,7, 11-trimethyl-2,6-dodecadiene (cis and trans-mixture).Boiling point 99-100 C./0.002 mm. Hg; n =1.475l.

The starting material is obtained as follows:

4.8 g. of sodium hydride (50% Nujol suspension) is washed twice withhexane and overlaid with 57 ml. of absolute tetrahydrofuran. Withstirring and ice-cooling, 5.8 g. allyl alcohol is added dropwise, andthe mixture is further stirred at room temperature for 1 hour. 28.5 g.farnesyl bnomide (cis and trans-mixture) and 40 ml.hexamethyl-phosphoric acid-triamide are subsequently, successively addeddropwise, and the mixture is stirred at room temperature for 2 hours andworked up as described in Example 1. By chromatography on Kieselgel withhexane and diethyl ether (9:1 parts by volume) is obtained pure allyl(3,7,11-trimethyl-2,6,IO-dOdecatrienyD-ether (cis and trans-mixture).Boiling point 94-95 C./.001 mm. Hg; n =1.4807.

To a homogeneous solution of 14.5 g. allyl-(3,7,11- trimethyl 2,6,10dodecatrienyD-ether (cis and transmixture) in ml. tetrahydrofuran and 25ml. water is added portionwise with ice-cooling 12.4 g.N-bromosuccinimide. The mixture is further stirred under ice-cooling for6 hours and worked up as described in Example 1. By chromatography onKieselgel with hexane and diethyl ether (4:1 parts by volume) isobtained pure 3-bromo-2,6,10-trimethyl-12-allyloxy-6,10-dodecadiene-2-ol (cis and trans-mixture)11 1.5022.

Example 13 A solution of 650 mg. sodium in 16 ml. absolute methanol isadded dropwise with ice-cooling to a solution of 9.33 g. 4- bromo 3,7,11trimethyl-13-allyloxy-7,1l-tridecadien-3-ol (cis and trans-mixture) in16 ml. absolute methanol, and the mixture is subsequently furtherstirred for 1 hour. The reaction mixture is poured onto ice-water,exhaustively extracted with diethyl ether and worked up as described inExample 1. By chromatography on Kieselgel with hexane and diethyl ether(4:1 parts by volume), there is obtained pure 1 (allyloxy) 10,11epoxy-3,7, 1l-trimethyl-2,6-tridecadiene (cis and trans-mixture).Boiling point ca. 120 C./.005 mm. Hg; (bulb-tube). n 1.4768.

The starting material is obtained as follows:

4.5 g. sodium-hydride (50% Nujol suspension) is washed twice with hexaneand overlaid with 17 ml. of absolute tetrahydrofuran. With stirring andcooling, 20.2 g. 3,7,11 trimethyl 2,6,10-tridecatriene-l-ol (cis andtrans-mixture) is added dropwise, and the mixture is further stirred for1 hour at room temperature. 10.9 g. allylbromide and 34 ml. hexamethylphosphoric acid triamide are subsequently, successively added dropwise,and the mixture is further stirred at room temperature for 16 hours andworked up as described in Example 1. By chromatography on Kieselgel withhexane and diethyl ether 4:1 parts by volume) is obtained pure ally1-(3,7,1 1- trimethyl 2,6,10 tridecatrienyl)-ether (cis and transmixture).Boiling point 87 C./ .001 mm. Hg; n =1.48l3.

8.9 g. N-bromosuccinimide is added portionwise with ice-cooling to ahomogeneous solution of 13.8 g. allyl- (3,7,l1trimethyl-2,6,10-tridecatrienyl)-ether (cis and trans-mixture) in 145ml. tetrahydrofuran and 23 ml. water. The mixture is further stirredwith ice-cooling for 6 hours and worked up as described in Example 1. Bychromatography on Kieselgel with hexane and diethyl ether (4:1 parts byvolume), there is obtained pure 4- bromo 3,7,11 trimethyl 13allyloxy-7,1l-tridecadiene-3-ol (cis and trans mixture). n =1.5030.

Example 14 A solution of 350 mg. sodium in 8.5 ml. absolute methanol isadded dropwise with ice-cooling to a solution of 5.08 g. 4 bromo 7ethyl-3,11-dimethyl-13-allyloxy- 7,11-tridecadien-3-ol (cis andtrans-mixture) in 8.5 m1. absolute methanol. The mixture issubsequently, further stirred for 1 hour, poured onto ice-water,exhaustively extracted with diethyl ether Worked up as described inExample 1. By chromatography on Kieselgel with hexane and diethyl ether(4:1 parts by volume), there is obtained pure 1 (allyloxy) 10,11 epoxy 7ethyl-3,1l-dimethyl-2,6-tridecadiene (cis and trans-mixture). Boilingpoint ca. 125 C./ .001 mm. Hg: n =1.4772.

The starting material is obtained as follows:

2.44 g. sodium hydride (50% Nujol suspension) is washed twice withhexane and overlaid with 11 ml. absolute tetrahydrofuran. With stirringand ice-cooling, a solution of 12.7 g.7-ethyl-3,11-dimethyl-2,6,IO-tridecatrien-lol (cis and trans-mixture) in11 ml. absolute tetrahydrofuran is added dropwise, and the mixture isfurther stirred at room temperature for 1 hour. 6.5 g. allylbromide and20 ml. hexamethylphosphoric acid triamide are subsequently successivelyadded dropwise, and the mixture is stirred at room temperature for 4hours and worked up as described in Example 1. By chromatography onKieselgel with hexane and diethyl ether (4:1 parts by volume), there isobtained pure allyl-(7-ethyl3,11-di-methyl-2,6,10 tridecatrienyl)-ether(cis and trans-mixture). Boiling point 93 C./ .001 mm. Hg; n =l.4800.

5.2 g. N-bromosuccinimide is added portionwise with ice-cooling to ahomogeneous solution of 8.34 g. allyl-(7- ethyl-3,11-dimethyl-2,6,l-tridecatrienyl)-ether (cis and trans-mixture) in 82ml. tctrahydrof-ur-an and 13 ml. water. The mixture is further stirredunder ice-cooling for 6 hours and worked up as described in Example 1.By chromatography on Kieselgel with hexane and diethyl ether (4:1 partsby volume), there is obtained pure 4- bromo 7ethyl-3,1l-dimethyl-l3-allyloxy-7,1l-tridecadiene-S-ol (cis andtrans-mixture). n =1.5019.

1 4 Example 15 Roundels (10 cm?) of cotton material are drenched with anacetonic solution of the active, allyl substances of the instantinvention and carefully dried. For each substance and concentration,30-60 freshly laid eggs of the Ephestia Ktlhniella are placed on theroundels and brought to hatching in a small cage of plastic at 25 C. andhigh humidity.

The action of the substances manifests itself in the premature orretarded death of the embryos in the egg or upon hatching. The resultsare expressed in percent egg mortality. The dosage is stated in: IO- g.of active substance/cm. of cotton material. Thus, dosage 3 means 10g./cm.

Example 16 An acetonic solution of the active substance of the instantinvention of known concentration is applied to the abdomen (ventral) ofTenebrio molitor pupae. The treated pupae are left at room temperaturefor 10 days in Petri dishes and thereafter examined as to whether adultanimals have developed from the pupae. The activity of the activesubstance is stated in percent inhibition of the development of adultanimals (AFI) (at the stated concentration) Concn. g. act. .AFI inSubstance subst. lpupa percentl-(allyloxy)-10,11-epoxy-3,7,1l-trlmethyl- {81. $8 2-cis/trans,fi-els-dodecadiene 5X10- 100 2X10- 60 We claim: 1. A compound of theformula:

wherein R and R are methyl or ethyl; R is methyl; R is hydrogen ormethyl; R R and R are hydrogen or lower alkyl; and m is 0 or 1.

2. The compound of claim 1 wherein R is hydrogen.

3. The compound of claim 2 wherein said compound is 1(allyloxy)-10,11-epoxy-3,7,ll-trimethyl-2,6-dodecadiene.

4. The compound of claim 2 wherein said compound is l- (allyloxy-6,7-epoxy-3,7-dimethyl-2-octene.

5. The compound of claim 2 wherein said compound is1-(allyloxy)-10,11-epoxy 3,7,10,11 tetramethyl-2,6- dodecadiene.

6. The compound of claim 2 wherein said compound is l-(allyloxy) 10,11epoxy 3,7,11 trimethyl-2,6-tridecadiene.

7. The compound of claim 2 wherein said compound is 1-(allyl0xy),- 10,11ep0Xy-7-ethy1 3,11 dimethyl- 2,6 tridecadiene NORMA S. MILESTONE, PnmaryExaminer 8. The compound of claim 2 wherein said compound U.S. C1. X.R.is 6,7 epoxy 3,7 dimethyl 1 [(1,1-dimethy1-2-pro- No references cited.

5 260-240 H, 410.9 N, 611 A, 614 R; 424-278, 312. 340. penyl) -oXy]-2-octene.

342, Dig. 12

